1. Field of the Invention
This invention relates to chemical compounds of the peptide type produced by synthetic methods and includes various processes.
2. Description of the Prior Art
Bestatin is a chemical active as an inhibitor of certain enzymes which was originally produced by fermentation of Streptomyces olivoreticuli as disclosed in various patents (see Farmdoc 09548X) and the following publications:
1. Umezawa, H.; T. Aoyagi, H. Suda, M. Hamada & T. Takeuchi: Bestatin an Inhibitor of Aminopeptidase B, Produced by Actinomycetes. J. Antibiotics 29:97-99, 1976. PA1 2. Suda, H.; T. Takita, T. Aoyagi & H. Umezawa: The Structure of Bestatin. J. Antibiotics 29:100-101, 1976. PA1 3. Nakamura, H.; H. Suda, T. Takita, T. Aoyagi, H. Umezawa & Y. Iitaka: X-Ray Structure Determination of (2S,3R)-3-amino-2-hydroxy-4-phenylbutanoic Acid, a New Amino Acid Component of Bestatin. J. Antibiotics 29:102-103, 1976. PA1 4. Suda, H.; T. Takita, T. Aoyagi and H. Umezawa: The Chemical Synthesis of Bestatin. J. Antibiotics 29:600-601, 1976. PA1 5. Umezawa, H.; M. Ishizuka, T. Aoyagi and T. Takeuchi, Enhancement of Delayed-Type Hypersensitivity by Bestatin, an Inhibitor of Aminopeptidase B and Leucine Aminopeptidase, J. Antibiotics 29, 857-859, 1976. PA1 R.sup.2 is (lower)alkyl having 1 to 6 carbon atoms, hydroxy(lower)alkyl, alkylthioalkyl, carboxamido(lower)alkyl, carboxy(lower)alkyl, phenyl or benzyl provided that when R.sup.1 is benzyl and R.sup.2 is isobutyl the configuration of the compound is (2S,3R,2'R), (2S,3S,2'S) or (2S,3S,2'R). PA1 R.sup.2 is (lower)akyl having 1 to 6 carbon atoms, hydroxymethyl, methylthioethyl, --CH.sub.2 CH.sub.2 CONH.sub.2, --CH.sub.2 CH.sub.2 COOH, phenyl or benzyl provided that when R.sup.1 is benzyl and R.sup.2 is isobutyl the configuration of the compound is (2S,3R,2'R), (2S,3S,2'S) or (2S,3S,2'R). PA1 R.sup.2 is (lower)alkyl having 1 to 6 carbon atoms, hydroxymethyl, methylthioethyl, --CH.sub.2 CH.sub.2 CONH.sub.2, --CH.sub.2 CH.sub.2 COOH, phenyl or benzyl. PA1 R.sup.2 is (lower)alkyl having 1 to 6 carbon atoms, hydroxymethyl, methylthioethyl, --CH.sub.2 CH.sub.2 CONH.sub.2, --CH.sub.2 CH.sub.2 COOH, phenyl or benzyl. PA1 R.sup.2 is (lower)alkyl having 1 to 6 carbon atoms, hydroxymethyl, methylthioethyl, --CH.sub.2 CH.sub.2 CONH.sub.2, --CH.sub.2 CH.sub.2 COOH, phenyl or benzyl provided that when R.sup.1 is benzyl and R.sup.2 is isobutyl the configuration of the compound is (2S,3R,2'R), (2S,3S,2'S) or (2S,3S,2'R). PA1 R.sup.2 is (lower)alkyl having 1 to 6 carbon atoms, hydroxymethyl, methylthioethyl, --CH.sub.2 CH.sub.2 CONH.sub.2, --CH.sub.2 CH.sub.2 COOH, phenyl or benzyl. PA1 R.sup.2 is (lower)alkyl having 1 to 6 carbon atoms. PA1 R.sup.2 is (lower)alkyl having 1 to 6 carbon atoms provided that when R.sup.1 is benzyl and R.sup.2 is isobutyl the configuration of the compound is (2S,3R,2'R), (2S,3S,2'S) or (2S,3S,2'R).
Bestatin has the chemical name [(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]-L-leucine and the following structure ##STR1##